1. Istituto di Ricerca Pediatrico Fondazione Città della Speranza, Padova Italy;
2. Clinica di Oncoematologia Pediatrica, Azienda Ospedaliera-Università di Padova, Padova, Italy;
3. Onco-hematology Unit, Az Ospedaliero-Universitaria di Ferrara S.Anna;
4. Pediatric Hematology and Oncology Unit, A.R.N.A.S. Ospedali Civico, Di Cristina e Benfratelli, Palermo, Italy;
5. Department of Radiotherapy, Centro di Riferimento Oncologico, Aviano, Pordenone, Italy; on behalf of the Linfoma non-Hodgkin and Linfoma di Hodgkin Working Groups AIEOP (Associazione Italiana Emato-Oncologia Pediatrica).
Background: Extracellular circulating DNA (cfDNA) can be found in small amounts in plasma of healthy individuals. Increased levels of cfDNA have been reported in patients with cancer of breast, cervix, colon, liver and it was shown that cfDNA can originate from both tumour and non-tumour cells.
Objectives: Levels of cfDNA of a large series of children with lymphoma were evaluated and analyzed in relation with clinical characteristics.
Methods: plasma cfDNA levels obtained at diagnosis in 201 paediatric lymphoma patients [43 Hodgkin lymphomas (HL), 45 anaplastic large cell lymphomas (ALCL), 88 Burkitt lymphomas (BL), 17 lymphoblastic (LBL), 8 diffuse large B cell lymphoma (DLBCL)] and 15 healthy individuals were determined using a quantitative PCR assay for POLR2 gene and, in addition, for NPM-ALK fusion gene in ALCL patients. Wilcoxon rank sum test was used to compare plasma levels among different patient subgroups and controls and to analyze relationship between levels of cfDNA and clinical characteristics.
Results: Levels of cfDNA in lymphoma patients were significantly higher compared with controls (p<0.0001). CfDNA was associated with median age (p=0.01) in HL, and with stage in ALCL (p=0.01). In HL patients high cfDNA levels were correlated with poor prognosis (p=0.03). In ALCL we found that most of the cfDNA (77%) was non-tumor DNA.
Conclusion: level of plasma cfDNA might constitute an important non-invasive tool at diagnosis in lymphoma patients' management; in particular in patients with HL, cfDNA seems to be a promising prognostic biomarker.
Keywords: lymphoma, childhood, cfDNA, prognosis, Hodgkin.